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Biomedical subjects

Alexander M Walker

Publications and source records attributed to Alexander M Walker.

At least 37 records · Page 2Linked to original sources
PubMed2005

Compliance with a statin treatment in a usual-care setting: retrospective database analysis over 3 years after treatment initiation in health maintenance organization enrollees with dyslipidemia.

BACKGROUND: Patients treated in a usual-care setting often do not comply with prescribed treatment regimens as closely as those treated in a clinical trial, for a variety of reasons. OBJECTIVES: We sought to describe compliance over 3 years with a statin treatment in an observational study in a usual-care setting and to investigate potential risk factors for poor compliance. METHODS: Enrollees in a Massachusetts health maintenance organization (HMO) who presented with baseline low-density lipoprotein cholesterol (LDL-C) > or =130 mg/dL and who started statin treatment between January 1, 1994, and July 1, 1999, were followed until death, termination of membership in the HMO, or July 1, 1999, whichever came first, as documented by the HMO's drug-dispensing electronic records. The records included information about the demographics, service dates, laboratory data, and filled prescriptions. The outcome measures were time to treatment discontinuation, time to treatment resumption, and adherence to treatment. RESULTS: A total of 4776 enrollees were included in the analysis. Most patients were aged 50 to 69 years (57%), men (52%), had LDL-C > or =160 mg/dL (77%), and received their prescription for antihyperlipidemia therapy from an internist or family physician (87%). The hazard of discontinuation was high during the first 6 months of therapy, with 20% of the initial population discontinuing treatment during this time period, then decreased, so that the fraction of continuing users leveled off: 74%, 65%, and 61% of statin initiators were still on treatment 1, 2, and 3 years after entry, respectively. The probability of resuming statin treatment was 51% within 24 months after last prescription filled. The proportion of adherent users stayed stable, between 53% and 55%, after the first 6 months. Risk factors of treatment discontinuation, treatment resumption, and adherence were remarkably similar and were stable over time. The significant predictors of treatment discontinuation were age <50 years (hazard ratio [HR], 1.45 [95% Cl, 1.26-1.68]), female sex (HR, 1.18 [95% CI, 1.06-1.30], and previous antihyperlipidemia treatment (HR, 0.71 [95% CI, 0.63-0.79]). CONCLUSIONS: In this HMO setting, women and individuals 1026 aged <50 years were at risk for poor compliance with statin therapy. Our analysis suggests that the association between compliance and age or gender may be quite stable over the first 3 years of treatment.

Age Factors↗
PubMed2005

The risk of nonvertebral fracture related to inhaled corticosteroid exposure among adults with chronic respiratory disease.

OBJECTIVE: To examine nonvertebral fracture risk in relation to inhaled corticosteroid (ICS) exposure among adults with respiratory disease. DESIGN AND PATIENTS: Nested case-control study within a cohort of 89,877 UnitedHealthcare members aged > or = 40 years with physician insurance claims for COPD or asthma, enrolled for > or = 1 year from January 1, 1997 to June 30, 2001. METHODS: Cases (n = 1,722) represented patients with a first treated nonvertebral fracture (the index date is the first fracture claim). Control subjects (n = 17,220) were randomly selected from the person-time and assigned a random index date. ICS exposure was ascertained 1 month, 3 months, 6 months, and 12 months before the index date, with estimated cumulative dose through 0 to 6 months, 7 to 12 months, and 0 to 12 months. Covariates included demographics, oral corticosteroid and other medication exposure, comorbidities, and indicators of respiratory disease severity. Odds ratios (ORs) adjusted for all covariates were estimated by logistic regression. RESULTS: No increased fracture risk with ICS exposure as a class or with fluticasone propionate alone was detected. ORs for exposure in the preceding 30 days were 1.05 (95% confidence interval [CI], 0.89 to 1.24), 1.13 (95% CI, 0.90 to 1.40), and 0.97 (95% CI, 0.78 to 1.21) for all ICS, fluticasone propionate, and other ICS, respectively. No dose-response effect was present. Among patients with COPD only (n = 6,932), no increased risk was found for recent ICS exposure (OR, 0.86; 95% CI, 0.59 to 1.25). CONCLUSIONS: Concern about nonvertebral fracture risk should not strongly influence the decision to use recommended doses of ICS for adult patients with asthma or COPD in managed-care settings in the United States. This study could not evaluate very-high ICS dose, long-term ICS exposure, or vertebral fracture risk.

Adult↗
PubMed2004

Benzodiazepine use and hip fractures in the elderly: who is at greatest risk?

BACKGROUND: It remains unclear whether benzodiazepine use increases hip fracture incidence. We studied this relationship in a large cohort, controlling for multiple potential confounders. METHODS: We analyzed 42 months of New Jersey Medicaid health care claims data for all enrollees. Each eligible person-day was assigned to categories of benzodiazepine exposure and categories of other predictors, based on prior and current medication dispensing and diagnosis information. Hip fractures were identified based on hospital claims with primary discharge diagnosis International Classification of Diseases, Ninth Revision (ICD-9) codes 820.xx. RESULTS: Cohort members (n = 125 203) contributed 194 071 person-years and had 2312 eligible hip fractures. After adjustment for age, sex, race, Medicaid nursing home residence, exposure to other psychoactive medications, including antiparkinsonian medications, diagnoses of epilepsy and dementia, and hospitalization in the previous 6 months, the incidence rate of hip fracture was significantly higher compared with no benzodiazepine use for exposure to any benzodiazepine (incidence rate ratio [IRR], 1.24; 95% confidence interval [CI], 1.06-1.44), to a short half-life, high-potency benzodiazepine (IRR, 1.27; 95% CI, 1.01-1.59), during the first 2 weeks after starting a benzodiazepine (IRR, 2.05; 95% CI, 1.28-3.28), during the second 2 weeks after starting a benzodiazepine (IRR, 1.88; 95% CI, 1.15-3.07), and for continued use (IRR, 1.18; 95% CI, 1.03-1.35). CONCLUSIONS: The incidence of hip fracture appears to be associated with benzodiazepine use. Contrary to several previous studies, short half-life benzodiazepines are not safer than long half-life benzodiazepines. Hip fracture risk is highest during the first 2 weeks after starting a benzodiazepine and declines thereafter.

Aged↗
PubMed2004

Incidence of thrombotic thrombocytopenic purpura/hemolytic uremic syndrome.

BACKGROUND: Thrombotic thrombocytopenic purpura and hemolytic uremic syndrome are rare disorders characterized by platelet aggregation, microthrombi, and resulting tissue damage. We studied the incidence and possible risk factors for these diseases in 3 large populations in the United States, United Kingdom, and Canada. METHODS: Data were derived from a large health insurer in the United States, general practices in the United Kingdom, and the Province of Saskatchewan. We identified potential cases of thrombotic thrombocytopenia purpura and hemolytic uremic syndrome in computerized data and verified them by medical record review. We estimated incidence rates for thrombotic thrombocytopenia purpura and hemolytic uremic syndrome together and separately, and we conducted a case-control study to evaluate potential risk factors. RESULTS: The age-sex standardized incidence of thrombotic thrombocytopenia purpura and hemolytic uremic syndrome was higher than previously reported (6.5, 2.2, and 3.2 per million per year in the United States, United Kingdom, and Saskatchewan, respectively), but there was no secular trend. The incidence of thrombotic thrombocytopenia purpura and hemolytic uremic syndrome was higher in women than men. Most cases of hemolytic uremic syndrome occurred before 20 years of age. We confirmed several known risk factors for thrombotic thrombocytopenia purpura and hemolytic uremic syndrome (cancer, bone marrow transplantation, pregnancy). CONCLUSION: The incidence of thrombotic thrombocytopenia purpura and hemolytic uremic syndrome is higher than previously reported but does not appear to be rising. Apparent international differences in incidence could be the result of imprecision in identifying thrombotic thrombocytopenia purpura and hemolytic uremic syndrome in large research databases.

Adult↗
PubMed2004

Serious cardiovascular events and mortality among patients with schizophrenia.

This study compared the risks of cardiovascular morbidity and mortality in people with schizophrenia who use antipsychotic medications to risks in individuals without schizophrenia in a large managed care organization. A sample of 1920 schizophrenia patients was matched by age, sex, date, and health plan to 9600 persons randomly selected from the health plan general membership. Death, myocardial infarction, arrhythmia, and new-onset diabetes were identified using a National Death Index search and medical claims records. The adjusted all-cause mortality rate in the group of treated schizophrenics was four times higher than in the control group regardless of whether patients were given a typical or an atypical antipsychotic medication. Users of typical antipsychotics had a fivefold higher risk of myocardial infarction than the control subjects. Among patients with schizophrenia, cardiovascular risk was inversely associated with intensity of use of antipsychotic drugs, suggesting that the observed risks may not be due to a simple or direct effect of drugs. Patients treated for schizophrenia had higher rates of new-onset diabetes than did the general population controls. This risk was most pronounced in persons with more intense exposure to drugs and appeared to be indistinguishable in users of typical antipsychotics, of atypical products, or of both.

Adult↗
PubMed2004

Occurrence of colon ischemia in relation to irritable bowel syndrome.

OBJECTIVE: In November 2000, alosetron HCl (Lotronex), a treatment for irritable bowel syndrome (IBS), was removed from the U.S. market in part because of the occurrence of colon ischemia in treated patients. Since the relation between colon ischemia and IBS is poorly understood, we evaluated the incidence of colon ischemia among people with and without IBS. METHODS: Using medical claims data from a large health care organization in the United States, we identified 87,449 people with an IBS diagnosis between January 1995 and December 1999. We calculated age- and sex-specific incidence rates in the general population and in IBS patients. RESULTS: There were 740 cases of colon ischemia during 8.5 million person-years of observation in 5.4 million persons. The crude incidence rate was 42.8 cases per 100,000 person-years for IBS patients. By comparison, the incidence rate was 7.2 per 100,000 person-years in the general population. After adjustment for age, sex, and calendar year, the incidence of colon ischemia in people with IBS was 3.4 times higher than in persons without (95% CI 2.6-4.5). CONCLUSIONS: Rates of colon ischemia among patients carrying a diagnosis of IBS are substantially higher than in the general population. Colon ischemia, though unusual in IBS patients, may nonetheless constitute a distinct part of the IBS natural history. Alternatively, it may be a consequence of therapy, or a manifestation of other bowel pathology that is sometimes confused with IBS.

Adult↗
PubMed2004

Risk factors for colon ischemia.

BACKGROUND: To identify predictors of colon ischemia, we examined demographic and clinical characteristics of patients, as well as their prior health care utilization. METHODS: Using insurance data, we identified 700 persons at least 20-yr old with presumed colon ischemia between 1995 and 1999, and 6,440 controls. Case identification was based on diagnosis and procedure codes in insurance claims for which we used a previously reported, validated algorithm. We ascertained preceding medical diagnoses and the use of drugs and health services from the insurance claims files. RESULTS: Patients with colon ischemia were nearly three times as likely to have IBS than controls. A history of nonspecific colitis, lower gastrointestinal tract hemorrhage, systemic rheumatologic disorders, and ischemic heart disease in the preceding 6 months, and abdominal surgery in the past month were also much more common in colon ischemia cases than controls. Use of a drug to treat diarrhea was strongly associated with risk. The most prevalent risk factor for colon ischemia was the use of drugs with a side effect of constipation, found in one-third of cases and one in nine controls. Cases had seen physicians, particularly gastroenterologists, much more commonly in the preceding 6 months than had controls. CONCLUSIONS: Clinically evident colon ischemia arises preferentially in persons with prior abdominal complaints, many of whom carry a diagnosis of IBS. Drugs that reduce bowel motility may constitute a widespread and potentially avoidable risk factor. The frequency of preceding doctor visits, without a specific diagnosis, suggests that colon ischemia may have a prolonged subacute presentation.

Adult↗
PubMed2003

A propensity score-matched cohort study of the effect of statins, mainly fluvastatin, on the occurrence of acute myocardial infarction.

This investigation quantified the effect of statins on acute myocardial infarction (AMI) in an observational setting where fluvastatin represented most of the statin use. The study applied propensity scores to match statin initiators to statin noninitiators and followed them for the occurrence of AMI. Serum low-density lipoprotein levels were reduced by statin therapy, and there were fewer incidents of AMI in statin initiators than in noninitiators.

Cholesterol, LDL↗
PubMed2003

Inhibition of clinical benefits of aspirin on first myocardial infarction by nonsteroidal antiinflammatory drugs.

BACKGROUND: There is clear evidence from numerous randomized trials and their meta-analyses that aspirin reduces risks of first myocardial infarction (MI). Recent data also suggest that other nonsteroidal anti-inflammatory drugs (NSAIDs) may interfere with this benefit of aspirin. METHODS AND RESULTS: We performed subgroup analysis from a 5-year randomized, double-blind, placebo-controlled trial of 325 mg aspirin on alternate days among 22 071 apparently healthy US male physicians with prospective observational data on use of NSAIDs. A total of 378 MIs were confirmed, 139 in the aspirin group and 239 in the placebo group. Aspirin conferred a statistical extreme (P<0.00001) 44% reduction in risk of first MI. Among participants randomized to aspirin, use of NSAIDs on 1 to 59 d/y was not associated with MI (multivariable adjusted relative risk [RR], 1.21; 95% confidence interval [CI], 0.78 to 1.87), whereas the use of NSAIDs on > or =60 d/y was associated with MI (RR, 2.86; 95% CI, 1.25 to 6.56) compared with no use of NSAIDs. In the placebo group, the RRs for MI across the same categories of NSAID use were 1.14 (95% CI, 0.81 to 1.60) and 0.21 (95% CI, 0.03 to 1.48). CONCLUSIONS: These data suggest that regular but not intermittent use of NSAIDs inhibits the clinical benefits of aspirin. Chance, bias, and confounding remain plausible alternative explanations, despite the prospective design and adjustment for covariates. Nonetheless, we believe the most plausible interpretation of the data to be that regular but not intermittent use of NSAIDs inhibits the clinical benefit of aspirin on first MI.

Adult↗
PubMed2003

Clinical and economic consequences of reference pricing for dihydropyridine calcium channel blockers.

OBJECTIVE: Reference pricing is a medication cost-sharing policy that fully covers medications which are less expensive than a standard reference price and requires patients to pay the extra cost of higher-priced drugs in a class of therapeutically substitutable drugs. Little information exists on the clinical and economic consequences. We analyzed changes in drug utilization, physician visits, hospitalizations, long-term care admissions, and expenditures after the introduction of reference pricing for dihydropyridine calcium channel blockers (CCBs) among patients aged 65 years or older in British Columbia, Canada. METHODS: This quasiexperimental longitudinal study was performed in the setting of Pharmacare, the state-funded drug benefits plan of all elderly persons in British Columbia. Study patients comprised all elderly residents of British Columbia who were enrolled in the provincial health insurance program and received dihydropyridine CCBs at the time of the policy change (35,886) and a subgroup of high-priced dihydropyridine CCB users (23,116). We studied the implementation of reference drug pricing on Jan 1, 1997, affecting all elderly Pharmacare beneficiaries. The main outcome measures were drug utilization, drug expenditures, physician visits, hospitalizations, long-term care, and net savings. RESULTS: The start of reference pricing was followed by a significant reduction in high-priced dihydropyridine CCBs (-150 monthly doses per 10,000 elderly persons), with a corresponding increase in fully covered dihydropyridine CCBs (+116). Overall, antihypertensive use did not decline (P =.46). Low-income status was a risk factor for discontinuing treatment (odds ratio, 1.64; 95% confidence interval [CI], 1.36 to 1.99); however, this was already observed to a similar magnitude 12 months before reference pricing (odds ratio, 1.46). In the overall study cohort, there was no increase in rates of physician visits, hospitalizations, and long-term care admissions. However, the 9% of patients who actually switched medications showed an 18% increase (95% CI, 8% to 28%) in physician visits and an increase of Canadian $13 (95% CI, Canadian $3 to Canadian $24) in costs of physician visits per patient as compared with nonswitchers during the transition but not afterward. This temporary increase may have been a result of additional prescribing and monitoring in switchers. Changes in drug expenditures and physician services resulted in net savings of Canadian $1.6 million in the first 12 months of policy implementation. CONCLUSIONS: Reference pricing as implemented in British Columbia may be a model for successful pharmaceutical cost-containment without adversely affecting patients or cost-shifting.

Aged↗
PubMed2003

Analgesic use and change in kidney function in apparently healthy men.

BACKGROUND: Studies using a single creatinine measurement have yielded inconsistent results regarding analgesic use and kidney function. METHODS: This is a prospective cohort study of 4,494 US male physicians who provided blood samples in both 1982 and 1996. Outcomes measured were increase in plasma creatinine level of 0.3 mg/dL or greater (> or =26.5 micromol/L) and decline in glomerular filtration rate (GFR) of 29.0 mL/min/1.73 m2 or greater during this 14-year period. Self-reported use of aspirin, acetaminophen, and other nonsteroidal anti-inflammatory drugs (NSAIDs) was classified as never (<12 pills during the study period), 12 to 1,499 pills, 1,500 to 2,499 pills, and 2,500 or greater pills during the study period. RESULTS: Blood measurements made 14 years apart showed increased creatinine levels in 242 participants and decreased GFRs in 224 participants. Compared with never use, multivariable-adjusted odds ratios (ORs) of increased creatinine levels were 0.98 (95% confidence interval [CI], 0.43 to 2.23) for 2,500 or greater pills of aspirin, 1.02 (95% CI, 0.55 to 1.90) for 2,500 or greater pills of acetaminophen, and 1.12 (95% CI, 0.67 to 1.87) for 2,500 or greater pills of other NSAIDs. For decreased GFRs, ORs for intake of 2,500 or greater pills were 0.75 (95% CI, 0.35 to 1.57) for aspirin, 1.22 (95% CI, 0.66 to 2.26) for acetaminophen, and 1.11 (95% CI, 0.65 to 1.90) for other NSAIDs. Use of aspirin, but not acetaminophen or other NSAIDs, was associated with a reduced risk for change in kidney function in participants without cardiovascular risk factors and a possible but nonsignificant increase in those with cardiovascular risk factors. CONCLUSION: Occasional to moderate analgesic intake of aspirin, acetaminophen, or NSAIDs does not appear to increase the risk for decline in kidney function during a period of 14 years.

Acetaminophen↗
PubMed2003

Incidence of colonic ischemia, hospitalized complications of constipation, and bowel surgery in relation to use of alosetron hydrochloride.

OBJECTIVE: Alosetron hydrochloride (Lotronex), a potent selective 5-hydroxytryptamine(3) receptor antagonist, was approved in February, 2000 in the United States for the treatment of diarrhea-predominant irritable bowel syndrome (IBS) in women. Marketing was suspended in November, 2000, after reports of colonic ischemia and serious complications of constipation. We sought to compare the incidence of colonic ischemia, hospitalized complications of constipation, and bowel surgery among alosetron users and a cohort of patients with IBS who did not use alosetron. METHODS: We sought outcomes of colonic ischemia, hospitalized complications of constipation, and bowel surgery in 3,631 Lotronex users and 2,480 comparison IBS subjects using diagnoses, procedures, and drugs recorded in the UnitedHealthcare insurance claims database, and validated these by chart review. The initial assessment was to last for 3 yr beginning with the start of alosetron treatment and was to include 10,000 Lotronex users; however, the observation period ended by December 31, 2000, after suspension of marketing. RESULTS: There were 3631 alosetron users among members of UnitedHealthcare from March through December, 2000, and we identified 2480 comparison IBS-only patients; follow-up time averaged about 5 months in both groups. There were no instances of colonic ischemia in either cohort. Thirty instances of bowel surgery occurred, giving rates of 10.2/1000 person-yr in the alosetron cohort and 11.8/1000 person-yr in the IBS/no alosetron cohort. There were three cases of hospitalized complications of constipation. The incidence rates were essentially the same in alosetron users (1.24/1000 person-yr) and in IBS patients with no alosetron use (0.92/1000 person-yr). CONCLUSIONS: Alosetron users did not differ from IBS patients not using alosetron in the incidence of bowel surgery or hospitalized complications of constipation; there were no cases of colonic ischemia. The statistical upper limit of colonic ischemia rates in alosetron users was 2.28/1000 person-yr. Because of the market withdrawal, the size of the cohort and the duration of follow-up were smaller than originally planned; consequently, the statements about the safety of alosetron were necessarily limited. On June 7, 2002, the Food and Drug Administration approved alosetron for reintroduction in the U.S. market for women with severe diarrhea-related IBS.

Adolescent↗
PubMed2002

The role of treatment intentions and concerns about side effects in women's decision to discontinue postmenopausal hormone therapy.

OBJECTIVES: To investigate the factors that influence women's decisions about hormone therapy use and the duration of use, in particular the effect of women's reasons for initiating hormone therapy, the source of information about hormones, women's symptom experience, and their concerns about side effects from hormone therapy. METHODS: Eight hundred and sixteen women aged 45-59 who began hormone therapy between July 1993 and June 1995 in a Massachusetts health maintenance organization were followed for two years from the day they received a prescription for estrogen. This cohort has been previously studied for health, treatment and demographic determinants of hormone therapy discontinuation. In March 1999, these women were mailed a questionnaire containing closed and open-ended questions. 449 women (55%) completed the survey. Discrete-time hazards models were used to identify determinants of discontinuation, controlling for medical predictors of survey nonresponse. RESULTS: Women's assessment of the difficulty of their decision to use hormone therapy (RR=1.25 for each point on a 7-point scale, 95% CI: 1.16, 1.35) was associated with discontinuation. Women who described their decision as extremely difficult had the greatest likelihood of discontinuing. The importance placed on preventing osteoporosis (RR=0.93 for each point on a 7-point scale, 95% CI: 0.86, 0.99) and cardiovascular disease (RR=0.94 for each point on a 7-point scale, 95% CI: 0.88, 0.99) were also statistically significant predictors of discontinuation. Women for whom the prevention of osteoporosis and cardiovascular disease were extremely important in deciding to use hormone therapy were the most likely to continue using hormones. Concerns about the return of monthly bleeding (RR=3.00, 95% CI: 1.45, 6.17) and weight gain (RR=2.06, 95% CI: 1.16, 3.67) at the time hormone therapy was initiated, but not the actual experience of these side effects while using hormones, were associated with a higher rate of discontinuation. Symptoms around the time of initiating hormone therapy, including the perceived severity of the symptom, were not statistically associated with discontinuation. CONCLUSIONS: Discontinuation of hormone therapy is the result of a complex process of decision-making that is influenced by the value placed on the prevention of osteoporosis and cardiovascular disease at the time of initiation and women's perceptions and interpretations of side effects. Concerns about the potential side effects of hormone therapy, in particular weight gain and monthly bleeding, lead women to discontinue hormone therapy.

Cardiovascular Diseases↗
PubMed2002

Impact of reference-based pricing for angiotensin-converting enzyme inhibitors on drug utilization.

BACKGROUND: Increasing copayments for higher-priced prescription medications has been suggested as a means to help finance drug coverage for elderly patients, but evaluations of the impact of such policies are rare. The objective of this study was to analyze the effect of reference-based pricing of angiotensin-converting enzyme (ACE) inhibitors on drug utilization, cost savings and potential substitution with other medication classes. METHODS: We analyzed 36 months of claims data from British Columbia for 2 years before and 1 year after implementation of reference-based pricing (in January 1997). The 119,074 patients were community-living Pharmacare beneficiaries 65 years of age or older who used ACE inhibitors during the study period. The main outcomes were changes over time in use of ACE inhibitors, use of antihypertensive drugs and expenditures for antihypertensive drugs, as well as predictors of medication switching related to reference-based pricing. RESULTS: We observed a sharp decline (29%) in the use of higher-priced cost-shared ACE inhibitors immediately after implementation of the policy (p < 0.001). After a transition period, the post-implementation utilization rate for all ACE inhibitors was 11% lower than projected from pre-implementation data. However, overall utilization of antihypertensives was unchanged (p = 0.40). The policy saved $6.7 million in pharmaceutical expenditures during its first 12 months. Patients with heart failure or diabetes mellitus who were taking a cost-shared ACE inhibitor were more likely to remain on the same medication after implementation of reference-based pricing (OR 1.12 [95% confidence interval, CI, 1.06-1.19] and 1.28 [95% CI 1.20-1.36] respectively). Patients with low-income status were more likely than those with high-income status to stop all antihypertensive therapy (OR 1.65 [95% CI 1.43-1.89]), which reflects a general trend toward discontinuation of therapy among these patients even before implementation of reference-based pricing. INTERPRETATION: Reference-based pricing in British Columbia achieved a sustained reduction in drug expenditures, and no changes in overall use of antihypertensive therapy were observed. Further research is needed on the overall health and economic effects of such policies.

Aged↗
PubMed2002

Outcomes of reference pricing for angiotensin-converting-enzyme inhibitors.

BACKGROUND: In January 1997, reference pricing for angiotensin-converting-enzyme (ACE) inhibitors for patients 65 years of age or older was introduced in British Columbia, Canada. For medications within a specific class, insurance covers the cost up to the reference price, and patients pay the extra cost of more expensive medications. Although reference pricing may reduce the costs of prescription drugs, there is concern that patients may switch to less effective medications or stop treatment. METHODS: We analyzed data from the Ministry of Health on all 37,362 residents of British Columbia who were 65 or older and were enrolled in the provincial health insurance program, received ACE inhibitors priced higher than the reference price of $27 a month in 1996, and were potentially affected by the new policy. We identified 5353 residents who switched to an ACE inhibitor not subject to cost sharing during the first six months and compared them with 27,938 residents who received only ACE inhibitors subject to cost sharing. RESULTS: Reference pricing for ACE inhibitors was not associated with changes in the rates of visits to physicians, hospitalizations, admissions to long-term care facilities, or mortality. The probability of stopping antihypertensive therapy decreased as compared with the probability before the change in policy (relative risk, 0.76; 95 percent confidence interval, 0.65 to 0.89). Eighteen percent of patients who had been prescribed ACE inhibitors subject to cost sharing switched to lower-priced alternatives. As compared with patients who did not switch, those who did had a moderate transitory increase in the rates of visits to physicians (rate ratio, 1.11; 95 percent confidence interval, 1.07 to 1.15) and hospital admissions through the emergency room (rate ratio, 1.19; 95 percent confidence interval, 0.99 to 1.42) during the two months after switching, but not subsequently. CONCLUSIONS: We found little evidence that when reference pricing for ACE inhibitors was introduced in British Columbia, patients stopped treatment for hypertension or that health care utilization and costs increased.

Aged↗
PubMed2002

Dopamine antagonists and the development of breast cancer.

BACKGROUND: Although animal studies have raised the possibility that prolactin-elevating dopamine antagonists used to treat psychotic disorders may initiate and promote breast cancers, epidemiologic studies in humans have been limited and inconsistent. METHODS: A retrospective cohort study was conducted of 52 819 women exposed and 55 289 not exposed to dopamine antagonists between January 1, 1989, and June 30, 1995. All participants were 20 years or older, initially free of breast cancer, and enrolled in the Medicaid or the Pharmaceutical Assistance to the Aged and Disabled programs of New Jersey. Incident breast cancer cases were identified through the New Jersey Cancer Registry and definitive breast cancer surgeries. Adjusted hazard ratios of breast cancer were calculated from multivariable proportional hazards models. RESULTS: Use of antipsychotic dopamine antagonists was associated with a 16% increase in the risk of breast cancer (adjusted hazard ratio, 1.16; 95% confidence interval, 1.07-1.26), with a dose-response relationship between larger cumulative dosages and greater risk. The increased risk was also seen in women who used prolactin-elevating antiemetic dopamine antagonists despite having different breast cancer risk profiles than antipsychotic dopamine antagonist users. Dopamine antagonist use was not associated with risk of colon cancer, a control condition not related to elevated prolactin levels. The increased risk of breast cancer among dopamine antagonist users was not explained by increased surveillance or protopathic bias. CONCLUSIONS: Antipsychotic dopamine antagonist use may confer a small but significant risk of breast cancer. In light of the small hazards and the possibility of residual confounding, these findings should lead to follow-up investigations but not to changes in treatment strategies.

Adult↗
PubMed2002

Serious ventricular arrhythmias among users of cisapride and other QT-prolonging agents in the United States.

PURPOSE: To evaluate the risk of serious ventricular arrhythmia (SVA) with cisapride use in the United States. METHODS: The study population included 28,078 patients under the age of 65 years who received cisapride between 1993 and 1998 with no history of antiarrhythmia treatment. Each follow-up day was classified according to use of cisapride and other factors. Outcomes of SVAs were identified using medical claims records and National Death Index search, and confirmed by medical record review. Rates of events were calculated for time on and off cisapride. Poisson regression analysis was used to calculate adjusted rate ratios. RESULTS: There were 23 cases of SVAs; 10 during periods of cisapride use and 13 during periods of non-use. The adjusted rate ratio comparing SVA events in cisapride use time to non-use time was 1.60 (95% CI: 0.67-3.82), and that identified for the other QT-prolonging drugs was 1.60 (95% CI: 0.65-3.98). CONCLUSIONS: The evidence for an increased risk of SVAs associated with cisapride was equivocal after taking observation time on and off cisapride into account, and adjusting for risk factors, though we cannot exclude the possibility of a 3.8-fold increased risk. Overall, the plausible risks of cisapride were similar to those of other QT-prolonging drugs.

Adolescent↗